壳聚糖/聚乙二醇/聚丙烯酸复合水凝胶的制备及药物控制释放行为研究

本文以壳聚糖(CS)、聚乙二醇(PEG)和丙烯酸(AA)为原料,制备了复合水凝胶CS/PEG/PAA。研究了负载四种具有不同结构和性质的药物(烟酸、烟酰胺、异烟肼和5-氟尿嘧啶)的复合水凝胶CS/PEG/PAA的药物控制释放行为。结果表明,烟酰胺和异烟肼在pH=1.80的缓冲溶液中的药物累积释放率(R)大于其在pH=6.86的缓冲溶液中的释放率;烟酸却在pH=6.86的缓冲溶液中的药物累积释放率(R)大于其在pH=1.80的缓冲溶液中的释放率。而5-氟尿嘧啶在两种缓冲溶液中的药物累积释放量相当。因此,复合水凝胶CS/PEG/PAA也许可以作为一种新型释放药物的载体。     

CO2致孔的海藻酸钠水凝胶对BSA的可控释放

本文以碳酸氢钠(NaHCO_3)为致孔剂制备了海藻酸钠/聚丙烯酸复合水凝胶(G-APCGs),采用扫描电子显微镜(SEM)观察了其形貌。水凝胶(G-APCGs)有清晰的孔洞结构,其结构受到单体和致孔剂投加量影响。进一步研究了丙烯酸(AA)、NaHCO_3投加量对复合水凝胶溶胀性能的影响。结果表明,复合水凝胶具有良好的pH敏感性。当海藻酸钠和AA质量比为1∶1.2时,G-APCGs溶胀度最大,可达209 g·g~(-1),且在6 h内达到溶胀平衡;NaHCO_3加入量为0.16 g时,G-APCGs的溶胀度最大,可达228 g·g~(-1)。G-APCGs负载BSA最大量为0.34 g·g~(-1)。负载BSA后的G-APCGs置于模拟胃液pH=1.2时,10 h内G-APCGs释放了7%的BSA;置于模拟肠液pH=7.5时,近85%的BSA在12 h内从G-APCGs中释放出来。     

pH敏感性P(AM-AA-co-C8PhEO10Ac)水凝胶溶胀动力学及其对茶碱的控释

以丙烯酰胺(AM)、丙烯酸(AA)和丙烯酸辛基酚聚氧乙烯醚酯(C8PhEO10Ac)为单体,采用自由基交联共聚法合成了具有pH敏感性的P(AM-AA-co-C8PhEO10Ac)水凝胶.研究了pH、单体配比对凝胶溶胀性能、溶胀动力学和退溶胀动力学的影响.初步探讨了模拟胃液(pH=1.4)、肠液(pH=7.4)中水凝胶对茶碱的控释情况.结果表明:凝胶具有高溶胀、退溶胀速率和良好的pH敏感性等特征;水凝胶的扩散行为在pH=7.4的缓冲溶液中为非Fickian扩散模式;载药凝胶在模拟肠液中对药物的累积释放率明显大于胃液中的累积释放率,其中n(C8PhEO10Ac)∶n(AM)∶n(AA)为1∶20∶30的载药水凝胶对茶碱的累积释放率最大.     

温度和pH敏感P(NIPA-co-AA)/粘土复合水凝胶的辐射制备与表征

以N-异丙基丙烯酰胺(NIPA)作为温敏性聚合单体,丙烯酸(AA)为pH敏感性单体,有机粘土为改性剂,采用~(60)Co-γ射线为辐射源,辐射合成了P(NIPA-co-AA),粘土复合水凝胶,研究了粘土的加入对水凝胶溶胀率、温度及pH敏感性和压缩性能的影响.结果表明,P(NIPA-co-AA)/粘土复合水凝胶的溶胀性能优于P(NIPA-co-AA)水凝胶,平衡溶胀率(SR)明显提高;且复合水凝胶仍表现出明显的温度和pH敏感性;粘土的加入提高了水凝胶的压缩强度、最大压缩力和压缩屈服力等力学性能,当粘土含量为15%时,P(NIPA-co-AA)/粘土复合水凝胶的压缩强度为P(NIPA-co-AA)共聚水凝胶的2.4倍,最大压缩力为P(NIPA-co-AA)的2.1倍.     

β-环糊精交联聚丙烯酸水凝胶的合成及其药物控制释放研究

采用1,3-二环己基碳化二亚胺(DCC)为缩合剂,通过β环糊精与丙烯酸的酯化反应合成了不同取代度的丙烯酸β环糊精酯(βCD6A),以此为单体与丙烯酸通过氧化还原自由基引发聚合,合成出了不同交联密度和不同环糊精含量的新型水凝胶(AAβCD6A).溶胀实验表明,该类水凝胶均具有pH敏感性,溶胀动力学实验进一步对其机理进行了探讨.选择苯丁酸氮芥(CHL)作为模型药物,考察了不同pH下AAβCD6A水凝胶对药物释放行为的影响.结果表明,pH=6.8时药物释放率均大于pH=2.0时药物释放率,环糊精的存在表现出促释作用.     

PVA/P(AA-AM)水凝胶的制备及药物控制释放性能研究

以聚乙烯醇(PVA)、丙烯酸(AA)和丙烯酰胺(AM)为单体,过硫酸铵(APS)为引发剂、N,N'-亚甲基双丙烯酰胺(MBA)为交联剂,通过化学引发聚合制备互穿水凝胶PVA/P(AA-AM);用红外光谱(IR)、热重分析(TG)、差示扫描量热法(DSC)及扫描电镜(SEM)等测试方法对其进行了表征,并对其溶胀性能、p H敏感性以及离子强度对溶胀性能的影响进行了研究;并考察了该凝胶分别在p H=6.86和p H=1.80介质中对药物异烟肼和烟酸的控制释放行为。结果表明,PVA/P(AA-AM)水凝胶具有良好的p H、离子强度敏感性,在两种介质中异烟肼的累积释放率均高于烟酸,但异烟肼在p H=1.80的介质中的释放速度和累积释放率均高于其在p H=6.86的介质,烟酸则结果恰好相反。所以这种水凝胶有望用作靶向药物释放的载体。     

可酶降解的温度及pH敏感水凝胶的制备及对牛血清白蛋白的吸附和释放

以4,4'-二甲基丙烯酰氨基偶氮苯(BMAAB)为偶氮交联剂,制备了可酶降解的N-异丙基丙烯酰胺(NIPAAm)-丙烯酸(AA)共聚物水凝胶. 结果表明,研究的凝胶均表现出在4 ℃和37 ℃之间的溶胀相转变. 以牛血清白蛋白(BSA)为模型药物,在pH=7.4的缓冲溶液中对BSA进行了负载. 结果表明,凝胶在4 ℃时对BSA的负载量为144.5 mg(BSA)/g(gel),37 ℃为14.8 mg(BSA)/g(gel). 凝胶在pH=7.4的缓冲溶液中,在结肠菌作用下能发生酶降解,药物累积释放量4 d可达100 mg(BSA)/g干胶.     

基于Pickering乳液的磁性高强水凝胶的制备及性能表征

合成了一种磁性Fe3O4纳米颗粒稳定的水包油(O/W)Pickering乳液并以其作为交联剂,在适宜条件下引发单体丙烯酰胺聚合来制备了一种新型的磁性高强复合水凝胶.采用X射线衍射(XRD)及场发射扫描电子显微镜(SEM)分别对磁性Fe3O4纳米颗粒和复合水凝胶的结构进行了表征,结果表明Pickering乳胶粒子较均匀地分布在复合凝胶网络中.溶胀性能测试及溶胀动力学分析表明复合水凝胶具有良好的溶胀性能,能够吸收自身干重100倍左右的水,其溶胀过程不遵循Fickian扩散模型;拉伸测试表明该水凝胶具有优异的力学性能,其拉伸强度能够达到150 kPa左右,断裂伸长率能够达到300%左右,并且当其承受的应力释放后能快速地恢复到初始形态.磁性能测试的结果显示该水凝胶具有良好的磁性.     

快速pH响应丝胶/聚甲基丙烯酸互穿网络水凝胶的合成及表征

采用同步互穿网络方法制备丝胶蛋白(SS)/聚甲基丙烯酸(PMAA)为组分的互穿网络(IPN)水凝胶. 研究了互穿网络水凝胶对介质pH的刺激响应性能. 结果表明, IPN水凝胶具有强烈的pH刺激响应性能. 在pH=9.2的缓冲溶液中, -COOH解离成 -COO^-, 渗透压与网络之间的静电排斥作用导致IPN的溶胀度增大; 当pH减小时, 溶胀度随之减小. IPN水凝胶具有快速退溶胀速率及可逆溶胀-收缩性能.     

麦饭石含量对载药复合凝胶小球释药性能的影响

以瓜尔胶-g-聚丙烯酸/麦饭石复合水凝胶(GG-g-PAA/MS)和海藻酸钠(SA)为原料,双氯芬酸钠(DS)为模拟药物,采用离子凝胶法制备了载药复合凝胶小球,考察了pH敏感性以及MS含量对复合凝胶小球的包封率、载药率、溶胀性和药物释放行为的影响.结果表明:凝胶小球具有明显的pH敏感性,在不同pH介质中溶胀率和释放速率...     

Radiation synthesis of superabsorbent poly(acrylic acid)–carrageenan hydrogels

A series of superabsorbent hydrogels were prepared from carrageenan and partially neutralized acrylic acid by gamma irradiation at room temperature. The gel fraction, swelling kinetics and the equilibrium degree of swelling (EDS) of the hydrogels were studied. It was found that the incorporation of even 1% carrageenan (sodium salt) increases the EDS of the hydrogels from 320 to 800 g/g. Thermal analysis were carried out to determine the amount of free water and bound water in the hydrogels. Under optimum conditions, poly(acrylic acid)–carrageenan hydrogels with high gel fraction (80%) and very high EDS (800 g/g) were prepared gamma radiolytically from aqueous solution containing 15% partially neutralized acrylic acid and 1–5% carrageenan. The hydrogels were also found to be sensitive to the pH and the ionic strength of the medium.     

pH快速响应PNIPAAm-co-PAAc水凝胶的制备及溶胀动力学

pH快速响应PNIPAAm-co-PAAc水凝胶的制备及溶胀动力学;N-异丙基丙烯酰胺;pH敏感性;溶胀历史     

Designing of pH-responsive ketorolac tromethamine loaded hydrogels of alginic acid: Characterization,in-vitro and in-vivo evaluation

pH-responsive hydrogels based on alginic acid grafted with acrylic acid and ethylene glycol dimethylacrylate in the presence of ammonium persulfate were developed for controlled delivery of Ketorolac tromethamine. The alginic acid based hydrogels were prepared by free radical polymerization technique. Increase in gel fraction was observed with the increase in alginic acid, acrylic acid, and ethylene glycol dimethylacrylate content. The dynamic swelling and drug release studies were conducted at two different pH values (pH 1.2 and 7.4). Maximum swelling and drug release were observed at pH 7.4. The characterization of prepared hydrogels was carried out by using Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, powder x-ray diffraction, and scanning electron microscopy. Similarly, in-vivo study was performed on rabbits and greater plasma drug concentration was achieved by fabricated hydrogels as compared to drug solution and commercial product Keten. Conclusively, the fabricated hydrogels can be considered as a potential candidate for controlled delivery of Ketorolac tromethamine.     

羧甲基纤维素与丙烯酸接枝共聚凝胶的溶胀动力学及过溶胀平衡特性的研究

采用接枝共聚合成了羧甲基纤维素钠、丙烯酸与N,N′-亚甲基双丙烯酰胺的交联凝胶, 研究了这类凝胶在不同pH值的缓冲溶液中的溶胀行为, 发现在酸性介质中凝胶的溶胀动力学行为表现出过溶胀平衡特性(overshooting effect), 即凝胶先发生溶胀到最大值, 然后再逐渐消溶胀到平衡. 这种现象可归因于凝胶溶胀过程中羧基之间通过氢键所产生的协同物理交联. 较之凝胶的组成, 缓冲溶液的pH值对过溶胀平衡现象的影响更为显著. 前者是因为凝胶羧基的总摩尔分数并不随两组分结构单元摩尔数的改变而改变, 羧基之间通过氢键形成的物理交联程度在交联剂摩尔分数接近的条件下变化不大; 后者是由于溶液的pH值显著影响凝胶羧基的质子化程度, 进而影响羧基之间通过氢键形成的物理交联程度. 凝胶在酸性介质中的溶胀过程符合E. Díez-Peña等提出的溶胀动力学定量模型, 理论曲线与实验数据有较好的相关性. 凝胶在pH≥5.0的缓冲溶液中的溶胀不产生过溶胀平衡现象, 这一现象归因于完全离子化的羧基之间不能形成物理交联. 凝胶的溶胀过程遵循Schott二级溶胀动力学.     

Synthesis,characterization, and evaluation of enzymatically degradable poly(N‐isopropylacrylamide‐co‐acrylic acid) hydrogels for colon‐specific drug delivery

The enzymatically degradable poly(N‐isopropylacrylamide‐co‐acrylic acid) hydrogels were prepared using 4,4^′‐bis(methacryloylamino)azobenzene (BMAAB) as the crosslinker. It was found that the incorporated N‐isopropylacrylamide (NIPAAm) monomer did not change the enzymatic degradation of hydrogel, but remarkably enhanced the loading of protein drug. The hydrogels exhibited a phase transition temperature between 4°C (refrigerator temperature) and 37°C (human body temperature). Bovine serum albumin (BSA) as a model drug was loaded into the hydrogels by soaking the gels in a pH 7.4 buffer solution at 4°C, where the hydrogel was in a swollen status. The high swelling of hydrogels at 4°C enhanced the loading of BSA (loading capability, ca. 144.5 mg BSA/g gel). The drug was released gradually in the pH 7.4 buffer solution at 37°C, where the hydrogel was in a shrunken state. In contrast, the enzymatic degradation of hydrogels resulted in complete release of BSA in pH 7.4 buffer solution containing the cecal suspension at 37°C (cumulative release: ca. 100 mg BSA/g gel after 4 days). Copyright © 2008 John Wiley & Sons, Ltd.     

离子键交联的聚两性电解质凝胶在不同pH和不同电解质溶液中溶胀行为研究

以丙烯酸(AA)和甲基丙烯酸二乙氨基乙酯(DEAM)形成的离子复合物与丙烯酰胺(AAm)共聚,合成了一种新型的离子键交联的聚两性电解质凝胶(PADA).由于分子之间的氢键作用,PADA凝胶并不是在A/C(负正离子单体摩尔比)为1,而是在A/C为1.55处有最大消溶胀.与共价键交联的聚两性电解质凝胶相比,PADA凝胶的溶胀行为具有更强的pH敏感性.PADA凝胶在不同pH缓冲溶液中的溶胀行为表明,在pH 3~4之间消溶胀程度最大.在偏离该pH区域时凝胶均发生溶胀.但凝胶的溶胀程度在pH<3的酸性溶液中随A/C的增加而降低;而在pH>4的偏碱性溶液中随其增加而增加.在不同价数的离子溶液中,离子浓度对于PADA凝胶的平衡溶胀有着不同的影响.对于一价的NaCl溶液,PADA凝胶有典型的反聚电解质效应.但对于高价的CaCl2和柠檬酸三钠溶液,只在较低的浓度下,才表现出反聚电解质效应.而在较高盐浓度时,随盐浓度的增加其溶胀比反而降低.这可能与高价离子形成的离子键交联有关.与pH对PADA凝胶溶胀程度的影响相似,在CaCl2溶液中,PADA凝胶的溶胀程度随A/C的增加而降低;而在柠檬酸三钠溶液中则刚好相反.这种独特的溶胀行为似乎与高价离子电荷的正负性有关.     

羧甲基壳聚糖水凝胶制备及其在药物控释中的应用

以戊二醛为交联剂制备了一系列羧甲基壳聚糖pH敏感水凝胶 .研究了合成条件对羧甲基壳聚糖水凝胶溶胀性能的影响 .实验结果表明羧甲基壳聚糖的脱乙酰度、交联剂用量对水凝胶溶胀率的影响较大 .pH=3 0时 ,水凝胶收缩 ,而pH =1 0 ,5 0 ,7 4 ,9 0时 ,水凝胶溶胀 ,且在碱性条件下水凝胶的溶胀率远大于酸性条件下的溶胀率 .包埋在此水凝胶中的水杨酸释放随载药介质的pH值和水凝胶半径大小的变化而显著不同 ,pH =1 0条件下载药的水凝胶的释药率大于pH =7 4 ,12 0条件下的释药率 ,且水凝胶的半径越大 ,释药速度和释药率也越大     

Synthesis of Carboxymethyl Cellulose Based Drug Carrier Hydrogel Using Ionizing Radiation for Possible Use as Site Specific Delivery System

A unique natural polymer based colon specific drug carrier was prepared from carboxymethyl cellulose (CMC) and acrylic acid (AAc) in aqueous solution employing γ‐radiation induced copolymerization and crosslinking. The effect of preparation conditions such as the natural polymer content and irradiation dose on gelation process was investigated. The swelling behavior of the prepared hydrogels was characterized by investigating the time and pH dependent swelling of the (CMC/AAc) hydrogels of different CMC content. The effects of the hydrogel composition and pH of the swelling medium on the swelling indices were estimated. The results show that the increment in the CMC content in the feed solution enhances the gelation process. The results also show the dependence of the swelling indices on both hydrogel composition and pH value of the swelling medium. To evaluate the ability of the prepared hydrogel to be used as a colon‐specific drug carrier, the release profile of theophylline was studied as a function of time at pH 1 and pH 7.     

Konjac glucomannan‐graft‐acrylic acid hydrogels containing azo crosslinker for colon‐specific delivery

In this article, the synthesis and characterization of novel hydrogel systems designed for colon‐targeting drug delivery are reported. The gels were composed of konjac glucomannan, copolymerized with acrylic acid, and crosslinked by the aromatic azo agent bis(methacryloylamino)‐azobenzene. The influence of various parameters on the dynamic and equilibrium swelling ratios (SRs) of the hydrogels was investigated. It is shown that the SR was inversely proportional to the grafting degree of acrylic acid and the content of bis(methacryloylamino)‐azobenzene. The dependence of SR on the pH indicates that obtained hydrogels are potential for drug delivery to colon. It was possible to modulate the degree of swelling and the pH sensitivity of the gels by changing crosslinking density of the polymer. The main chain of hydrogels can be degraded by β‐glycosidase which is abundant in colon. They can be in vitro degraded for 73% in a month by Cereflo® and 86% in 20 days by Mannaway25L. We have also prepared the hydrogels that loaded with bovine serum albumin about 1.5%, 3%, 9%, and 20% by weight. In vitro release of model drug bovine serum albumin was studied in the presence of Mannaway25L or Fungamyl®800L in pH 7.4 phosphate buffer at 37 °C. The drug release can be controlled by the biodegradation of the hydrogels. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4370–4378, 2004